ArticleNature communications2019
Dehydration and insulinopenia are necessary and sufficient for euglycemic ketoacidosis in SGLT2 inhibitor-treated rats.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 5 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 5 syntheses or guidelines pooled it, 103 citations in OpenAlex.
- SGLT2 inhibitor therapy following aortic valve intervention for aortic stenosis: a systematic review and meta-analysis of mortality, heart failure, rhythm, renal, and valve-related outcomes.Journal of cardiothoracic surgery · 2026Pooled it
- The Effects of SGLT2 Inhibitors on Muscle Health in Older Adults: A Systematic Review and Meta-Analysis.Pharmacology research & perspectives · 2026Pooled it
- iCatCare 2025 consensus guidelines on the diagnosis and management of diabetes mellitus in cats.Journal of feline medicine and surgery · 2025Guideline
- What is the utility of blood beta-hydroxybutyrate measurements in emergency department in patients without diabetes: a systematic review.Systematic reviews · 2023Pooled it
- Assessing the risk of ketoacidosis due to sodium-glucose cotransporter (SGLT)-2 inhibitors in patients with type 1 diabetes: A meta-analysis and meta-regression.PLoS medicine · 2020Pooled it
- Safety and Short-Term Effects of Empagliflozin in Patients with Heart Failure and End-Stage Renal Disease.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2026Trial
- Basal insulin secretion capacity predicts the initial response and maximum levels of beta-hydroxybutyrate during therapy with the sodium-glucose co-transporter-2 inhibitor tofogliflozin, in relation to weight loss.Diabetes, obesity & metabolism · 2020Trial
- Article
- Ferroptosis regulation by SGLT2 inhibitors: mechanisms and clinical benefits in diabetic kidney disease.Frontiers in pharmacology · 2026Review
- SGLT2 Inhibitors: From Structure-Effect Relationship to Pharmacological Response.International journal of molecular sciences · 2025Review
- Sodium-glucose co-transporter 2 inhibitors: Prospects for canine myxomatous mitral valve disease and finding the "right drug" and the "right dose" for dogs.The Journal of veterinary medical science · 2025Review
- Concurrent SGLT2 inhibitor use in patients with type 2 diabetes hospitalised for high-dose corticosteroid therapy: Mitigated iatrogenic hyperglycaemia.Diabetes, obesity & metabolism · 2025Article
- Dehydration-induced AVP stimulates glucagon release and ketogenesis.American journal of physiology. Endocrinology and metabolism · 2025Article
- A kidney-hypothalamus axis promotes compensatory glucose production in response to glycosuria.eLife · 2024Article
- From Sweet to Sour: SGLT-2-Inhibitor-Induced Euglycemic Diabetic Ketoacidosis.Journal of personalized medicine · 2024Review
- Risk of Diabetic Ketoacidosis Associated with Sodium Glucose Cotransporter-2 Inhibitors: A Network Meta-Analysis and Meta-Regression.Journal of clinical medicine · 2024Review
- Empagliflozin improves cardiac function in rats with chronic heart failure.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Sodium-Glucose Cotransporter-2 Inhibitor-Induced Euglycemic Diabetic Ketoacidosis in a Type 2 Diabetic Patient.Cureus · 2023Article
- Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes.Circulation · 2023Review
- Empagliflozin-associated postoperative mixed metabolic acidosis. Case report and review of pathogenesis.BMC endocrine disorders · 2023Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Sodium-glucose transport protein 2 (SGLT2) inhibitors are a class of anti-diabetic agents; however, concerns have been raised about their potential to induce euglycemic ketoacidosis and to increase both glucose production and glucagon secretion. The mechanisms behind these alterations are unknown. Here we show that the SGLT2 inhibitor (SGLT2i) dapagliflozin promotes ketoacidosis in both healthy and type 2 diabetic rats in the setting of insulinopenia through increased plasma catecholamine and corticosterone concentrations secondary to volume depletion. These derangements increase white adipose tissue (WAT) lipolysis and hepatic acetyl-CoA content, rates of hepatic glucose production, and hepatic ketogenesis. Treatment with a loop diuretic, furosemide, under insulinopenic conditions replicates the effect of dapagliflozin and causes ketoacidosis. Furthermore, the effects of SGLT2 inhibition to promote ketoacidosis are independent from hyperglucagonemia. Taken together these data in rats identify the combination of insulinopenia and dehydration as a potential target to prevent euglycemic ketoacidosis associated with SGLT2i.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.